Nonlinear correlation between serum vitamin D levels and the incidence of endometrial polyps in infertile women.

Study question: Are serum vitamin D levels associated with the incidence of endometrial polyps (EPs) in infertile patients?

Summary answer: Serum 25(OH)D levels were nonlinearly correlated with the incidence of EPs in infertile women.

What is known already: EPs are a common condition that may affect the receptivity of the endometrium in women of reproductive age. Vitamin D regulates cell proliferation and differentiation, apoptosis, angiogenesis, anti-inflammation, and immunomodulation, in addition to its well-known functions in balancing calcium and phosphorus. Previous studies have shown that vitamin D concentrations are associated with reproductive outcomes, and that low vitamin D levels are associated with the incidence of colorectal polyps and nasal polyps. There is little evidence regarding the relationship between EPs and serum vitamin D levels.

Study design, size, duration: We conducted a cross-sectional study using data from Guangdong Women and Children Hospital from January 2019 to October 2023, enrolling 3107 patients.

Participants/materials, setting, methods: A total of 3107 infertile patients who underwent hysteroscopy were included in this study; 642 patients had endometrial polyps and 2465 had a normal uterine cavity. Hysteroscopy findings included risk of EPs, polyp size, percentage of multiple polyps, and incidence of chronic endometritis (CE). Serum vitamin D were assessed by measuring total 25(OH)D using chemiluminescence. According to international guideline recommendations for vitamin D deficiency, patients were divided into two groups: the <50 nmol/l group and the ≥50 nmol/l group. Univariable and multivariable logistic regression models, stratified analyses, and smooth curve fitting were used to examine the relationship between serum 25(OH)D levels and risk of EPs.

Main results and the role of chance: Of all patients, 23.8% (740/3107) were vitamin D deficient (<50 nmol/l). The incidence of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group (24.9% vs 19.3%; P = 0.001). However, there were no differences in polyp size, proportion of multiple polyps, and presence of CE between the two groups. After controlling for confounders, 25(OH)D ≥ 50 nmol/l (compared with <50 nmol/l) was negatively associated with risk of EPs (adjusted OR, 0.733; 95% CI, 0.598-0.898). Other variables that had an impact on polyp incidence included BMI, type of infertility, CA125, and CD138-positive plasma cells. In addition, a linear regression model between age and serum 25(OH)D levels showed a positive linear association. Subgroup analyses were performed for different age groups, and the risk of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group, both in the younger subgroup (23.8% vs 19.1%) and in the older subgroup (28.0% vs 19.9%). The smooth curve fitting model showed a nonlinear correlation between 25(OH)D levels and risk of EPs (nonlinear P-value = 0.020), with an optimal threshold of 51.8 nmol/l for 25(OH)D levels. Moreover, subgroup smooth curve fitting models showed a nonlinear correlation between 25(OH)D levels and polyp risk in patients aged <35 years (nonlinear P-value = 0.010), whereas a linear correlation between 25(OH)D levels and polyp risk was found in patients aged ≥35 years (nonlinear P-value = 0.682).

Limitations, reasons for caution: Caution should be exercised in interpreting our findings as this is a correlational study and causality cannot be inferred from our results. In addition, because of strict inclusion and exclusion criteria, our results may not be generalizable to unselected populations, including premenopausal women or women of other races.

Wider implications of the findings: This study demonstrated for the first time that vitamin D deficiency is an independent risk factor for the incidence of EPs in infertile patients. Identifying modifiable risk factors (e.g. vitamin D deficiency) can help in the development of new strategies for treating polyps or to protect against polyp development. Further clinical intervention trials and laboratory studies are needed to evaluate the effect of vitamin D on the development of EPs and to elucidate the mechanisms.

Study funding/competing interest(s): The study was funded by the National Natural Science Foundation of China (82101718) and Natural Science Foundation of Guangdong Province, China (2022A1515010776). No competing interest was involved in this study.

Trial registration number: N/A.